The field of this invention is the regulation of menstrual cycles, including the control of ovulation, contraception, and ovarian hormone production. The most relevant prior art relates to the contraception drug anordrin.
Anordrin is an A-nor steriod developed in China as an oral contraceptive. See, Ku et al, Scientia Sinica, Vol. XVIII, No. 2, 262-270 (1975). When anordrin is synthesized, it is obtained in the form of a mixture of two isomers. The .alpha.-form isomer is 2.alpha., 17.alpha.-diethynyl-A-nor-5.alpha.-androstane-2.beta.,17.beta.-diol dipropionate, and the .beta.-form isomer is 2.beta.,17.alpha.-diethynyl-A-nor-5.alpha.-androstane-2.alpha.,17.beta.-di ol dipropionate. As indicated by Ku et al, above cited, the 60 , .beta.-isomer mixture has been used in China as an oral contraceptive, and referred to as AF-53, or as Anti-Fertility Tablet No. 53.
The .beta.-isomer has a lower level of activity with respect to ovarian functions than the .alpha.-isomer. The .alpha.-isomer anordrin can be readily separated from the .beta.-isomer to obtain the .alpha.-anordrin as a pure crystalline compound. See, for example, Mehta, et al, Steroids, Vol. 38, No. 6, pages 679-691, at 680 (1981).
Researchers in the People's Republic of China have studied the endometrial and hormonal changes induced by .alpha.,.beta.-anordrin in women using post-menstrual pre-ovulatory regimens of oral administration with varying dose levels and administration schedules. See Hu et al, WHO Symposium on Steroid Contraception and Mechanisms of Endometrial Bleeding, E. Diczfalusy et al (eds) Geneva, 12-14 Sept., 1979, pages 191-200. Hu et al concluded from the data presented that ovulation can be inhibited and/or luteal function depressed when administration of anordrin is started in the period following menstruation but prior to ovulation. It was observed that when anordrin is started up to three days prior to ovulation that ovulation may be inhibited, and that a suppressive effect on the development of Graafian follicles may be observed. Hu et al, above cited, page 198.
Chen, C. H. and Chen, Y. have published a study of urinary pregnanediol measurements following .alpha.,.beta.-anordrin administration to women postmenses, using varying dose levels and administration procedures. Chinese J. Obset. and Gynecol. 3: 85-88 (1978). The doses of .alpha.,.beta.-anordrin varied from 0.5 mg to 4 mg per day, starting from 1 to 6 days after menstruation and continuing for 7 to 9 continuous days. The administration procedures included an intravaginal capsule, a suppository capsule, and an oral capsule. The study confirmed that .alpha.,.beta.-anordrin administered during the phase of follicular development could inhibit ovulation. The study also indicated that the time of ovulation could be determined by measurements of urinary pregnanediol. Urine collections were continued following the last dose of the .alpha.,.beta.-anordrin until menstruation occurred; a delay in ovulation occurred in only about 10% of women in these studies.